Formulations containing melatonin, ginkgo biloba, and biotin

ABSTRACT

The present invention relates to a composition which comprises as active ingredients a combination of melatonin,  ginkgo biloba  and biotin. The composition is particularly suitable for producing formulations for topical application in the hair.

CROSS REFERENCE TO RELATED APPLICATION

This application is a 35 USC §371 National Phase Entry Application fromPCT/EP03/012097, filed Oct. 30, 2003, designating the United States,which is a continuation-in-part of U.S. Ser. No. 10/353,056 filed Jan.29, 2003.

The present invention relates to a composition which comprises as activeingredients a combination of melatonin, ginkgo biloba and biotin. Thecomposition is particularly suitable for producing formulations fortopical application in the hair.

The use of melatonin for beneficially influencing hair growth is known.Melatonin has a stimulating effect on hair growth due to the selectiveinteraction with proliferating cells of the hair follicles which controlthe growth of hair. This stimulating effect can be observed with the useof different concentrations of melatonin.

U.S. Pat. No. 5,952,373 describes a method for the treatment of skin, inwhich a composition which comprises as active ingredient one or moreflavonoids is applied. There is no reference to the use of melatonin asactive ingredient for improving hair growth.

US patent application US 2002/0061870 discloses a composition for theamelioration of hearing loss or tinnitus. This composition, which isadministered in form of a tablet, comprises a large number of activeingredients, optionally also including melatonin, biotin or ginkgobiloba. There is no reference to the use for improving hair growth or totopical application.

It has surprisingly been found in the investigations leading to thepresent invention that the addition of ginkgo biloba and biotin insimultaneous use of melatonin enhance the effect of melatonin, andretention of melatonin on the surface of the scalp is increased.

One aspect of the present invention is thus a composition whichcomprises as active ingredients (a) melatonin or a derivative thereof,(b) ginkgo biloba as extract or/and one or more constituents thereof and(c) biotin. The composition is preferably a topical formulation suitablefor pharmaceutical or/and cosmetic uses, in particular for applicationto the scalp.

The composition of the invention comprises a combination of activeingredients. The first component of this combination is melatonin or amelatonin derivative. Melatonin derivatives are preferably selected from5-methoxytryptamine, 5-methoxytryptophan, 5-methoxytryptophol,5-methoxyindole-3-acetic acid and 6-hydroxymelatonin. Besides thesesubstances it is also possible to employ physiologically acceptablesalts, esters and complex compounds thereof.

The second component of the composition is ginkgo biloba. Ginkgo bilobahas a beneficial influence on various metabolic functions. A furtheradvantageous property of ginkgo is the enhancement of the potential fortrapping free radicals. A ginkgo biloba is preferably used as extract,in particular as dry extract, or/and one or more constituents thereof.Dry extracts from ginkgo leaves are particularly suitable for use of thecomposition of the invention.

A further component of the composition of the invention is biotin.Biotin displays its effect for example as coenzyme in fatty acid andamino acid metabolism, e.g. in transcarboxylation reactions.

The concentration of the active ingredients in the composition can bevaried within wide limits—depending on the use. It is beneficial for theconcentrations of the active ingredients each to be independently in therange between 0.0001% (weight) to 1% (weight) based on the total weightof the composition. The concentration of melatonin or a melatoninderivative is preferably 0.001% (weight) to 0.01% (weight). Theconcentration of ginkgo biloba is preferably 0.01% (weight) to 0.1%(weight). The concentration of biotin is preferably 0.002% (weight) to0.05% (weight).

Preferably about 0.001 mg to about 10 mg, preferably about 0.01 mg toabout 1 mg, of melatonin or melatonin derivative are administered perapplication.

The three active ingredient components of the composition of theinvention display a profile of effects which promotes hair growth,provides protection from aging, improves hair thickness or/and reducesthe telogen rate. The effect of melatonin on the hair follicle issurprisingly enhanced by the combination with ginkgo biloba and biotin.It is thus possible to employ even very low concentrations of melatonin,for example about 0.001-10 mg, preferably about 0.01-1 mg perapplication, with a satisfactory effect.

The combination of melatonin, ginkgo biloba and biotin can beadministered in a suitable carrier system. The active ingredients arepreferably present as solution or/and dispersion in a liquid, semisolidor solid carrier system. Examples of suitable carrier systems areliquids such as water or aqueous buffer solutions, physiologicallytolerated organic solvents such as ethanol or combinations thereof,oil-water emulsions, water-oil emulsions, fats, polyethylene glycols,propylene glycols, glycerol, emulsifiers or combinations thereof, andother carriers or excipients used in pharmaceutical and cosmeticformulations.

The use of an aqueous carrier system, i.e. a carrier system with a watercontent of 50% (weight) or more, in particular of 60% (weight) or more,is preferred. The pH of an aqueous carrier system is preferably adjustedin a range between pH 3 and pH 6, particularly preferably in the rangefrom pH 3.5 and pH 4.

These carrier systems advantageously enable targeted delivery of theactive ingredients to the hair follicle. The placement of the activeingredients in the hair follicle is optimized thereby. Controlledabsorption of the melatonin, ginkgo biloba and biotin active ingredientscan moreover be made possible by the carrier system.

The processing of melatonin with ginkgo biloba and biotin in suitablecarrier systems may in addition lead to a prevention or delay ofmelatonin absorption. The normal human plasma level is not influencedthereby. In addition, a longer-lasting effect of the active ingredientscan be achieved.

Stable formulations used in cosmetics, especially in the form ofcosmetics solutions, can be obtained by formulation in a carrier system.

In the use of specific formulation systems such as liposomes, nanosomesor solid inclusion carriers such as agarose it is possible to obtaincompositions which permit controlled delivery of at least one of theactive ingredients, in particular of all the active ingredients.

The compositions of the invention are particularly suitable forpharmaceutical or/and cosmetic applications, for example in hair. Thecompositions may be in the form of a solution, suspension, emulsion,microemulsion, nanosystem, cream, gel, lotion, spray, foam or ointmentor any other form suitable for topical applications. They are normallyemployed in a packaging or application system selected from tubes,bottles, spray bottles, patches, sponges and textile or plasticscarriers and other systems suitable for application in the hair. Aparticularly preferred packaging system are single-dose ampules whichprovide a dosage unit for one application. The ampules may be fabricatedfrom various materials, e.g. from glass or plastics. Plastics ampulesare particularly preferred because plastics ampules ensure safe andsatisfactory handling.

Besides the active ingredients, the compositions of the invention maycomprise one or more cosmetic or/and pharmaceutical excipients oradditives, for example thickeners, minerals, oils, vitamins, e.g.vitamin A, especially in the form of retinoic acid, or fragrances.

The combination preparations of the invention are recommended inparticular for application in the evening and display their effect inparticular during the night. With this mode of application, the effectof the composition is particularly strong. The compositions of theinvention are particularly suitable for stimulation of the hairfollicles and a beneficial influence on hair growth.

The treatment takes place in particular in topical applications suitablefor use in the hair, which comprise the appropriate concentrationssuitable for the particular purpose of use of the active ingredients.

The composition of the invention can be employed for promoting hairgrowth, in particular for the prevention or/and treatment of alopecia inmen or in women. Particularly preferred indications are male-typeandrogenic alopecia, female-type androgenic alopecia, male-type diffusealopecia and female-type diffuse alopecia.

The invention is further illustrated by the following example.

EXAMPLE Composition of a Formulation of the Invention with the ActiveIngredients Melatonin, ginkgo biloba and Biotin

The composition comprises 0.05% by weight of ginkgo biloba dry extract,0.01% by weight of biotin, 0.0033% by weight of melatonin and furtheradditives, water and ethanol. The pH of the composition is between 3.5and 4.

1. A method of promoting hair growth on a subject in need of suchpromotion comprising applying to areas of the subject where hair growthis desired a composition comprising active ingredients and a carriersystem, wherein said active ingredients consist of (a) melatonin or aderivative thereof selected from the group consisting of5-methoxytryptamine, 5-methoxytryptophan, 5-methoxytryptophol,5-methoxyindole-3-acetic acid and 6-hydroxymelatonin, andphysiologically acceptable salts, esters and complex compounds thereof,(b) ginkgo biloba and (c) biotin.
 2. A method of claim 1, wherein thehair growth is promoted in the prevention and or treatment of alopecia.3. The method as claimed in claim 2, wherein the subject is a man. 4.The method as claimed in claim 2, wherein the subject is a woman.
 5. Themethod as claimed in claim 1, wherein from 0.001 mg to 10 mg ofmelatonin are administered per application.
 6. The method as claimed inclaim 5, wherein from 0.01 mg to 1 mg of melatonin are administered perapplication.
 7. The method according to claim 1, wherein said subject issuffering from androgenic or diffuse alopecia.
 8. A method of promotinghair growth on a subject in need of such promotion comprising applyingto areas of the subject where hair growth is desired, a compositioncomprising active ingredients, wherein said active ingredients consistof (a) melatonin or a derivative thereof selected from the groupconsisting of 5-methoxytryptamine, 5-methoxytryptophan,5-methoxytryptophol, 5-methoxyindole-3-acetic acid and6-hydroxymelatonin, and physiologically acceptable salts, esters andcomplex compounds thereof, (b) ginkgo biloba and (c) biotin.
 9. A methodof promoting hair growth on a subject in need of such promotioncomprising applying to areas of the subject where hair growth isdesired, a composition comprising (a) melatonin or a derivative thereofselected from the group consisting of 5-methoxytryptamine,5-methoxytryptophan, 5-methoxytryptophol, 5-methoxyindole-3-acetic acidand 6-hydroxymelatonin, and physiologically acceptable salts, esters andcomplex compounds thereof, (b) ginkgo biloba and (c) biotin, whereinsaid ginkgo biloba and said biotin are in amounts sufficient to delaythe absorption of said melatonin or derivative thereof.